The local immune response in the lung to infectious organisms is instrumental in preventing and limiting pulmonary infections. In addition, hypersensitivity reactions to inhaled antigens play a major role in producing significant pulmonary disease. The goal of this project is to determine the route and form of clearance of particulate antigen (the nonpathogenic virus, tobacco mosaic virus, TMV) from the broncho-alveolar spaces to local and systemic lymphoid tissue and to establish the relationship of antigen transport to the development of specific cell-mediated and humoral immunity. We will determine the rate of removal of radioactive antigen from broncho-alveolar spaces and relative uptake by local and systemic lymphoid tissue. Light and electron microscopic studies utilizing peroxidase-labeled antibodies and autoradiography will be used to determine whether degradation of intact viral particles occurs prior to transport across alveolar and /or respiratory epithelium, whether transepithelial antigen transport is predominantly intra or intercellular and whether pulmonary macrophages play a role in transport to local lymphoid tissue. Populations of cells derived from local and systemic lymphoid tissue will be analyzed for content of specific T cells by proliferative responses to antigen and for B cells by measuring plaque forming cells to determine the correlation between antigen deposition and the development of immune reactive lymphocytes. Finally, the effect of immunity on antigen redistribution and the localization of immune reactive cells will be studied in animals after a second intratracheal instillation in order to determine if antigen is more rapidly cleared or if it results in the emigration of additional antigen reactive cells into the lung.